Marie-France Poirier

Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors

The high-affinity binding sites for [3H]-imipramine (IMI) present in human platelets are associated with the neuronal uptake system for 5HT. It was recently demonstrated that previous antidepressant therapy with drugs which inhibit 5HT uptake could down-regulate [3H]-IMI binding and that this effect could persist up to 1 month after the end of treatment. We therefore re-examined the reported differences inBmax of [3H]-IMI binding in platelets between control and depressed untreated patients, to evaluate the residual influence of previous antidepressant medication. The saturation characteristics of [3H]-IMI binding were compared in platelets from 17 depressed patients care-fully selected according to previous antidepressant therapy and washout period, who were closely matched, for age and sex, with a group of control healthy volunteers. The results reveal a significant decrease by 47% in theBmax of [3H]-IMI binding in platelets of untreated depressed patients when compared with controls. There was no significant modification ofKd values for platelet [3H]-IMI binding between the depressed and the control groups. Our results support the view that platelet [3H]-IMI binding is a useful tool as a biological marker in depression.

Platelet 3H-imipramine binding and steroid hormones serum concentrations during the menstrual cycle

The presence of high affinity binding sites for 3H-imipramine (3H-IMI) in human platelets is by now well established. This recognition site is associated with the transporter for 5HT, and may be a biological marker in depression. Fluctuations of other putative biological markers of depression (i.e. platelet MAO activity) have been demonstrated and shown to be correlated with variations in steroid hormones. Therefore, the KD and Bmax of 3H-IMI binding was determined in platelets of young women during the menstrual cycle. Our results indicate that within the limits of intraindividual variations, neither the KD or the Bmax of 3H-IMI binding in platelets is significantly modified during the menstrual cycle.

Platelet Monoamine Oxidase Activity and Plasma 3,4-Dihydroxy-phenylethylene Glycol Levels during the Menstrual Cycle

The influence of endocrine factors on monoamine oxidase activity (MAO) and on noradrenaline metabolism has been evaluated by measuring platelet MAO activity and plasma levels of 3,4-dihydroxyphenylethylene glycol (DOPEG), the major deaminated metabolite of noradrenaline, as well as serum levels of steroid hormones weekly in 9 young healthy women during one menstrual cycle. A decrease in platelet MAO activity (correlated with high serum estradiol levels) was observed during the ovulatory period. In contrast, plasma free or sulfoconjugated DOPEG remained unchanged throughout the menstrual cycle. These results indicate that the hormonal status should be taken into consideration in studies dealing with platelet MAO activity in depressed women.

Natural autoantibodies in schizophrenia

Autoantibodies reacting with cell constituents other than antinuclear antibodies have seldom been reported in the literature on schizophrenia. Serum of 41 DSM‐III‐R schizophrenic patients was examined for the presence of various autoantibodies and compared with that of healthy volunteers (n= 10) and hospitalized controls. Titers of IgG, IgA and IgM autoantibodies directed against actin, tubulin, myosin, DNA, thyroglobulin, elastin, albumin, DNA and trinitrophenyl groups were determined using enzyme immunoassay. IgG and IgA titers were significantly decreased in schizophrenic patients. These results contrast with those obtained with various other autoimmune and nonautoimmune diseases in which titers are either unchanged or increased. A significant increase of various autoantibody levels was observed in the paranoid subgroup of schizophrenics compared with the disorganized subgroup. These autoantibodies possess characteristics similar to those of natural autoantibodies, which seem to play several biological roles.

Diagnostic and therapeutic value of testing stimulation of thyroid-stimulating hormone by thyrotropin-releasing hormone in 100 depressed patients

The thyrotropin‐releasing hormone (TRH) test was performed in 100 depressed patients, including 73 patients with a major depressive episode (MDE) according to DSM‐III. Thirty‐one patients subsequently received an antidepressant with a predominant serotoninergic action (indalpine or citalopram), and 27 patients received a noradrenergic antidepressant (maprotiline). The diagnostic value of the TRH test was not conclusive for any of the subgroups of depressed patients: MDE, MDE with melancholia or MDE in bipolar patients. Similarly, the value of the TRH test in the choice of antidepressant treatment according to the monoaminergic action was not convincing. These results are discussed in the light of the data of the international literature.

Platelet MAO activity in clinical subtypes of depression and DST suppression

ABSTRACT— Platelet MAO activity was measured in 75 hospitalized depressed patients and in 31 healthy subjects. Plasmas post dexamethasone cortisol levels were examined in 73 patients. Results indicate that higher platelet MAO activity does not occur in all, but only in male major depressed patients. No relationship between changes of MAO activity and specific clinical subtypes was found. Platelet MAO activity is not different between DST suppressors and DST non suppressors. The authors suggest that platelet MAO activity may be related to non specific factors such as sex, age, but not to diagnosis of depression.

Lack of correlation between DST results and urinary MHPG in depressed inpatients

Abnormalities of noradrenaline metabolism and of the activity of hypothalamic-pituitary adrenal axis (HPA) have been reported in depression. To study the possible relationship between these 2 parameters, urinary excretion of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and Dexamethasone Suppression Test (DST) were analyzed in 58 depressed patients. A positive correlation was found between the age of depressed patients and 24-h urinary excretion of MHPG. Twenty-two patients (38%) were DST non suppressors. Pre-DST plasma cortisol levels were significantly higher in non suppressors than suppressors. No difference was found however between urinary MHPG levels in supressors and non suppressors. There was no correlation between pre-DST plasma cortisol and levels of urinary excretion of MHPG. These results do not support the hypothesis of a relationship between these 2 parameters. However, when depressed patients were separated into two groups according to urinary excretion of MHPG (“high MHPG” and “low MHPG”), the “high MHPG” group included significantly more non suppressors then the “low MHPG” one. This result is not sufficient to demonstrate of link between HPA system activity and central noradrenaline metabolism.

Lack of circadian rhythm in plasma levels of 3,4-dihydroxyphenylethyleneglycol in healthy human subjects

In order to investigate the possible existence of a circadian rhythm in plasma free and sulfate-conjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the plasma levels of this metabolite (and for comparison, of melatonin and cortisol) were measured in seven healthy volunteers at 4-h intervals over a period of 24 h. Plasma concentrations of melatonin and cortisol showed distinct diurnal variations with acrophases at 2.5 h and 8.5 h, respectively. In contrast, plasma free DOPEG levels were relatively stable over the 24-h period studied. Sulfate-conjugated and free + sulfate-conjugated DOPEG levels showed a slight, non-significant increase in the early afternoon. These results indicate that in contrast to plasma 3-methoxy 4-hydroxyphenylethyleneglycol, plasma free and conjugated DOPEG levels do not exhibit a circadian rhythm.

Plasma 3,4-Dihydroxyphenylethyleneglycol and Therapeutic Response to Maprotiline and Indalpine in Major Depression

Plasma levels of free and conjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of norepinephrine, were assayed in 48 depressed patients before initiating a treatment with either maprotiline, an inhibitor of norepinephrine reuptake, or indalpine, a specific inhibitor of serotonin reuptake. The two groups of depressed patients were comparable. The therapeutic effect was evaluated by using the Hamilton Rating Scale for Depression. No difference in pretreatment plasma free and conjugated DOPEG levels was found between the responders and the nonresponders to maprotiline or indalpine. Neither was there any difference in the pretreatment levels of plasma free DOPEG between the two groups of responders and the two groups of nonresponders to either drug. Finally, there was no difference in the therapeutic response to maprotiline or to indalpine between the patients with high and low plasma DOPEG levels before treatment. These results indicate that there is no relationship between the initial plasma levels of DOPEG in depressed patients and their therapeutic response to a norepinephrine or a serotonin reuptake blocker.

Plasma 3,4-Dihydroxyphenylethyleneglycol Levels in Depressed Patients with and without Abnormal Dexamethasone Suppression

Escape from dexamethasone-induced suppression of plasma cortisol is an abnormality found in about half of patients with major depression. It has been hypothesized that this hyperactivity of the hypothalamo-pituitary-adrenal axis might be related to a central noradrenergic hypofunction. The present study was designed to test this hypothesis by measuring plasma 3,4-dihydroxyphenylethyleneglycol (DOPEG) levels (free and conjugated forms), an index of central noradrenergic activity, and by simultaneously carrying out a dexamethasone suppression test. Forty-five patients with a diagnosis of major depression (according to the DSM-III) were investigated. Plasma DOPEG levels (measured at 8 a.m.) were found to be similar in dexamethasone suppressor and nonsuppressor depressed patients. These results do not support the hypothesis that central noradrenergic hypoactivity underlies nonsuppression of dexamethasone in major depression.